Nasal Mucoadhesive in situ Gel of Ondansetron Hydrochloride

Indian Journal of Pharmaceutical Sciences 711 November December 2009 In conclusion, liposomal dispersion of FP was successfully prepared with more than 90% entrapment. Spray dried liposomes had mean size of 3-4 μ and FPF of 9-10%. Inclusion of antistatic agents such as leucine and magnesium stearate did not improve the aerosolisation behaviour of DPIs in this study. Further studies are warranted in order to improve the FPF.

Ondansetron hydrochloride is a serotonin (5HT 3 ) receptor antagonist used in the management of nausea and vomiting that is associated with cancer chemotherapy.There is a need for intranasal delivery due to poor bioavailability of drug because of first pass effect [1] .The objective of this study was to develop an intranasal delivery system of ondansetron hydrochloride using thermo sensitive polymer PF127 and mucoadhesive polymer.

MATERIALS AND METHODS
Lutrol F127 (PF127 and hydroxypropylcellulose (Klucel LF) was procured from Signet Chemicals Mumbai.Ondansetron hydrochloride was received as a gift sample from Dr. Reddy's Lab Hyderabad.
Nasal formulations consisting of aqueous gels of PF127 containing 18% (w/v) of polymer were prepared using the method described by Schmolka [2] .Composition was given in Table 1.The prepared formulations were evaluated for appearance, clarity, Government of India, for providing funds for the research work, TIFR Mumbai for XRD, Glenmark Pharmaceuticals, Mumbai for DSC, Cipla, Mumbai for drug gift sample.Propylene glycol (ml) 0.9 0.9 0.9 0.9 0.9 Transcutol-P (ml) 0. pH, gelation temperature, spredability, bioadhesion strength, viscosity, drug content and diffusion study.Gelation temperature (TG) was measured by visual inspection using a modifi cation of Miller and Donavan technique [3] .Rheological studies were performed using a Brookfield digital CAP 2000+ viscometer to determine viscosity.Spreadability in terms of flow ability of various mucoadhesive thermoreversible gels was determined [4] .The bioadhesive potential of each formulation was determined by measuring the weight required to detach the formulation from nasal mucosal tissue using a method described by Yong et al. [5] .
In vitro release studies were carried out in the following manner: A glass cup with a cross-sectional area of 7.5 cmnd and adhesive tape, and inverted under the surface of 500 ml of simulated nasal fl uid of pH 5.5 at 35±0.5° in USP XXIII Type I Dissolution Test Apparatus with a speed of 50 rpm.Five millilitres of aliquots were withdrawn at specifi ed time intervals and immediately replaced with fresh dissolution medium [6] .The drug content in the withdrawn samples was determined spectrophotometrically at 310 nm using a UV/Vis spectrophotometer and simulated nasal electrolyte solution as a blank.

RESULTS AND DISCUSSION
All gels were glassy clear in appearance.Gel pH was in the range of 5.3 to 5.6 which was in the range of pH at the absorption site (4.5-6.5).In the preliminary studies, the minimum concentration of PF127 that formed gel below 34 0 was found to be 18% wt/vol.The plain formulation (F1) without bioadhesive polymer has minimum bioadhesion 529.2 dyne/cm 2 but maximum spredability and 88.2% drug release after 8 h.In all formulations 0.2% w/v bioadhesive polymer showed maximum spredability while 0.7% w/v showed minimum spredability (Table 2).There was drastic increase in viscosity at gelation temperature (Table 3, fi g. 1).It was observed that the concentration of bioadhesive polymer increased from 0.2% to 0.7% showed retardation of ondansetron hydrochloride release from 75.2% to 54.9% (fi g. 2).did not vary more than ±1 0 .The gelation temperature lowering effect of bioadhesive polymer might have caused in part by the increased viscosity after dissolution of mucosadhesive polymer.The pH values of all formulations were found in the range of 5.3 to 5.6.Formulation should posses' mild acidic pH for activation of lysozyme (A natural antibacterial enzyme important for controlling nasal microbial count which becomes inactive at alkaline pH).The pKa of ondansetron hydrochloride is 7.4; so drug present in solubilised form in pH range 5 to 6.5 (ondansetron hydrochloride precipitate above 6.8).It was observed that the concentration of bioadhesive polymer increased from 0.2% to 0.7% showed retardation of ondansetron hydrochloride release, probable mechanism for such retardation of release may be reduction in number and dimensions of the channels in gel structure by increased viscosity of the formulation.From the study it can be concluded that the nasal in situ gels can be formulated of ondansetron hydrochloride using PF127 and bioadhesive polymer.